期刊
CURRENT OPINION IN RHEUMATOLOGY
卷 21, 期 5, 页码 471-477出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/BOR.0b013e32832e089e
关键词
interferon; lupus; plasmacytoid dendritic cells
类别
资金
- The Alliance for Lupus Research, the Swedish Research Council
- Dana Foundation
- Swedish Rheumatism Association
- Gustafsson Foundation
Purpose of review Patients with lupus have signs of an ongoing production of type I interferons (IFNs) that are of importance both for the etiopathogenesis and the clinical manifestations. In this review, we summarize the latest information concerning the type I IFN system in lupus. Recent findings Activated plasmacytoid dendritic cells are responsible for the IFN alpha production in lupus and can be found in target organs such as glomeruli. The plasmacytoid dendritic cells are triggered by interferogenic immune complexes, and produced IFN alpha activates the immune system and impairs T-regulatory cell function. Autoantibodies, which can form interferogenic immune complexes, are not only present in serum of lupus patients but also in the cerebrospinal fluid of patients with neuropsychiatric manifestations. There is a strong association between risk to develop lupus and gene variants connected to the production and effects of type I IFN. Risk variants can not only cause either increased serum IFN alpha activity or sensitivity but also a more severe disease phenotype. Administration of monoclonal anti-IFN alpha antibodies to lupus patients downregulates several proinflammatory pathways and reduces disease activity. Summary Increasing evidence indicates that the activated type I IFN system in lupus is critical in the etiopathogenesis of the disease and is an important therapeutic target.
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